Details
| Original language | English |
|---|---|
| Pages (from-to) | 41-52 |
| Number of pages | 12 |
| Journal | Acta biomaterialia |
| Volume | 68 |
| Early online date | 2 Dec 2017 |
| Publication status | Published - 1 Mar 2018 |
Abstract
The decellularization of biological tissues decreases immunogenicity, allows repopulation with cells, and may lead to improved long-term performance after implantation. Freeze drying these tissues would ensure off-the-shelf availability, save storage costs, and facilitates easy transport. This study evaluates the in vivo performance of freeze-dried decellularized heart valves in juvenile sheep. TritonX-100 and sodium dodecylsulfate decellularized ovine and porcine pulmonary valves (PV) were freeze-dried in a lyoprotectant sucrose solution. After rehydration for 24 h, valves were implanted into the PV position in sheep as allografts (fdOPV) and xenografts (fdPPV), while fresh dezellularized ovine grafts (frOPV) were implanted as controls. Functional assessment was performed by transesophageal echocardiography at implantation and at explantation six months later. Explanted grafts were analysed histologically to assess the matrix, and immunofluorescence stains were used to identify the repopulating cells. Although the graft diameters and orifice areas increased, good function was maintained, except for one insufficient, strongly deteriorated frOPV. Cells which were positive for either endothelial or interstitial markers were found in all grafts. In fdPPV, immune-reactive cells were also found. Our findings suggest that freeze-drying does not alter the early hemodynamic performance and repopulation potential of decellularized grafts in vivo, even in the challenging xenogeneic situation. Despite evidence of an immunological reaction for the xenogenic valves, good early functionalities were achieved. Statement of Significance: Decellularized allogeneic heart valves show excellent results as evident from large animal experiments and clinical trials. However, a long-term storing method is needed for an optimal use of this limited resource in the clinical setting, where an optimized matching of graft and recipient is requested. As demonstrated in this study, freeze-dried and freshly decellularized grafts reveal equally good results after implantation in the juvenile sheep concerning function and repopulation with recipients’ cells. Thus, freeze-drying arises as a promising method to extend the shelf-life of valvular grafts compared to those stored in antibiotic-solution as currently practised.
Keywords
- Decellularization, Freeze-drying, Heart valve replacement, Matrix-guided tissue regeneration
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biotechnology
- Materials Science(all)
- Biomaterials
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Engineering(all)
- Biomedical Engineering
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
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In: Acta biomaterialia, Vol. 68, 01.03.2018, p. 41-52.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - In vivo performance of freeze-dried decellularized pulmonary heart valve allo- and xenografts orthotopically implanted into juvenile sheep
AU - Goecke, Tobias
AU - Theodoridis, Karolina
AU - Tudorache, Igor
AU - Ciubotaru, Anatol
AU - Cebotari, Serghei
AU - Ramm, Robert
AU - Höffler, Klaus
AU - Sarikouch, Samir
AU - Vásquez Rivera, Andrés
AU - Haverich, Axel
AU - Wolkers, Willem F.
AU - Hilfiker, Andres
N1 - Publisher Copyright: © 2017 Acta Materialia Inc.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - The decellularization of biological tissues decreases immunogenicity, allows repopulation with cells, and may lead to improved long-term performance after implantation. Freeze drying these tissues would ensure off-the-shelf availability, save storage costs, and facilitates easy transport. This study evaluates the in vivo performance of freeze-dried decellularized heart valves in juvenile sheep. TritonX-100 and sodium dodecylsulfate decellularized ovine and porcine pulmonary valves (PV) were freeze-dried in a lyoprotectant sucrose solution. After rehydration for 24 h, valves were implanted into the PV position in sheep as allografts (fdOPV) and xenografts (fdPPV), while fresh dezellularized ovine grafts (frOPV) were implanted as controls. Functional assessment was performed by transesophageal echocardiography at implantation and at explantation six months later. Explanted grafts were analysed histologically to assess the matrix, and immunofluorescence stains were used to identify the repopulating cells. Although the graft diameters and orifice areas increased, good function was maintained, except for one insufficient, strongly deteriorated frOPV. Cells which were positive for either endothelial or interstitial markers were found in all grafts. In fdPPV, immune-reactive cells were also found. Our findings suggest that freeze-drying does not alter the early hemodynamic performance and repopulation potential of decellularized grafts in vivo, even in the challenging xenogeneic situation. Despite evidence of an immunological reaction for the xenogenic valves, good early functionalities were achieved. Statement of Significance: Decellularized allogeneic heart valves show excellent results as evident from large animal experiments and clinical trials. However, a long-term storing method is needed for an optimal use of this limited resource in the clinical setting, where an optimized matching of graft and recipient is requested. As demonstrated in this study, freeze-dried and freshly decellularized grafts reveal equally good results after implantation in the juvenile sheep concerning function and repopulation with recipients’ cells. Thus, freeze-drying arises as a promising method to extend the shelf-life of valvular grafts compared to those stored in antibiotic-solution as currently practised.
AB - The decellularization of biological tissues decreases immunogenicity, allows repopulation with cells, and may lead to improved long-term performance after implantation. Freeze drying these tissues would ensure off-the-shelf availability, save storage costs, and facilitates easy transport. This study evaluates the in vivo performance of freeze-dried decellularized heart valves in juvenile sheep. TritonX-100 and sodium dodecylsulfate decellularized ovine and porcine pulmonary valves (PV) were freeze-dried in a lyoprotectant sucrose solution. After rehydration for 24 h, valves were implanted into the PV position in sheep as allografts (fdOPV) and xenografts (fdPPV), while fresh dezellularized ovine grafts (frOPV) were implanted as controls. Functional assessment was performed by transesophageal echocardiography at implantation and at explantation six months later. Explanted grafts were analysed histologically to assess the matrix, and immunofluorescence stains were used to identify the repopulating cells. Although the graft diameters and orifice areas increased, good function was maintained, except for one insufficient, strongly deteriorated frOPV. Cells which were positive for either endothelial or interstitial markers were found in all grafts. In fdPPV, immune-reactive cells were also found. Our findings suggest that freeze-drying does not alter the early hemodynamic performance and repopulation potential of decellularized grafts in vivo, even in the challenging xenogeneic situation. Despite evidence of an immunological reaction for the xenogenic valves, good early functionalities were achieved. Statement of Significance: Decellularized allogeneic heart valves show excellent results as evident from large animal experiments and clinical trials. However, a long-term storing method is needed for an optimal use of this limited resource in the clinical setting, where an optimized matching of graft and recipient is requested. As demonstrated in this study, freeze-dried and freshly decellularized grafts reveal equally good results after implantation in the juvenile sheep concerning function and repopulation with recipients’ cells. Thus, freeze-drying arises as a promising method to extend the shelf-life of valvular grafts compared to those stored in antibiotic-solution as currently practised.
KW - Decellularization
KW - Freeze-drying
KW - Heart valve replacement
KW - Matrix-guided tissue regeneration
UR - http://www.scopus.com/inward/record.url?scp=85044730859&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2017.11.041
DO - 10.1016/j.actbio.2017.11.041
M3 - Article
C2 - 29191508
AN - SCOPUS:85044730859
VL - 68
SP - 41
EP - 52
JO - Acta biomaterialia
JF - Acta biomaterialia
SN - 1742-7061
ER -